CN1158567A - Compositions for the treatment of skin disorders - Google Patents

Compositions for the treatment of skin disorders Download PDF

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Publication number
CN1158567A
CN1158567A CN95195041A CN95195041A CN1158567A CN 1158567 A CN1158567 A CN 1158567A CN 95195041 A CN95195041 A CN 95195041A CN 95195041 A CN95195041 A CN 95195041A CN 1158567 A CN1158567 A CN 1158567A
Authority
CN
China
Prior art keywords
inhibitor
treatment
pharmaceutical composition
acne
lovastatin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN95195041A
Other languages
Chinese (zh)
Other versions
CN1106841C (en
Inventor
N·萨维昂
S·布伦纳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
RAMOT UNIV AUTHORITY FOR APPLIED RESEARCH AND INDUSTRIAL DEVELOPMENT Ltd
Ramot at Tel Aviv University Ltd
Original Assignee
RAMOT UNIV AUTHORITY FOR APPLIED RESEARCH AND INDUSTRIAL DEVELOPMENT Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by RAMOT UNIV AUTHORITY FOR APPLIED RESEARCH AND INDUSTRIAL DEVELOPMENT Ltd filed Critical RAMOT UNIV AUTHORITY FOR APPLIED RESEARCH AND INDUSTRIAL DEVELOPMENT Ltd
Publication of CN1158567A publication Critical patent/CN1158567A/en
Application granted granted Critical
Publication of CN1106841C publication Critical patent/CN1106841C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/08—Antiseborrheics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
    • A61K2800/782—Enzyme inhibitors; Enzyme antagonists

Abstract

An inhibitor of cholesterol synthesis is used for the treatment, alleviation or prevention of skin disorders.

Description

Treat dermopathic compositions
Invention field
The present invention relates to be applied to skin surface to improve the compositions field of skin.The invention provides and be used to improve the particularly method and composition of acne of various skins.Background of invention
Acne is the follicular chronic inflammatory disease of a kind of pilosebaceous unit, especially at face and cervical region, and most adolescence that occurs in about 14-19 year.Acne and sebum secretion thing increase, arterial cone hyperkeratosis under the folliculus pipe, and microorganism moves living increase and inflammation-related (Strauss, J.S., J.Dermatol.Treat. (treating skin disease magazine), 1:3-6 (1989)).People have proposed the method for multiple treatment acne and other sebaceous gland inflammation, from concrete diet, prevent that skin from contacting with the known preparation (as rudimentary cosmetics) of acne (acneignic) that causes, to the use that contains progesterone or estrogen and other hormone preparation, but the great majority in them also are not proved to be effective.In addition, people also advise using antiseptic, antibacterial and antibacterial compound in broad spectrum on surface and whole body.
Up to now, the development of the anti-acne formulations of all uses microbial population in suppressing sebaceous gland, the formation aspect of keratinization and acne all is effective.Yet, a few is only arranged to reducing effectively (Gollnick of sebum excretion rate in used up to now anti-acne formulations, H., J.Dermatol.Treat. (treating skin disease magazine), 1:S23-S28 (1990)), also be used to control the biosynthesis of lipid in the pilosebaceous unit unit without any preparation.
Can synthesize isoprenoid group such as cholesterol by the mevalonate approach, Squalene and cholesteryl ester (Goldstein, J.L., Brown, M.S., Nature (nature), 34B, 425 (1990)), wherein end-product is a cholesterol.Regulate the key enzyme of mevalonate preparation, the precursor of promptly above-mentioned isoprenoid group is 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.This kind of enzyme inhibitor has suppressed the synthetic of cholesterol, and therefore is used as treatment arteriosclerosis, the antihypercholesterolemic thing of hyperlipidemia and relevant disease.The example of this inhibitor has lovastatin (MerckIndex 5460, U.S.4,231,938).The pharmaceutical composition that contains the HMG-CoA reductase inhibitor can be used to suffer from arteriosclerosis or hyperlipidemia patient by the mode of oral or parenterai administration.
Summary of the invention
We find pleasantly surprisedly, use cholesterol synthetic inhibitor can treat acne according to the present invention by the surface.Therefore, purposes of the present invention is with cholesterol synthetic inhibitor treatment various skin disease.
The invention provides and be used for skin surface and contain carrier and as the compositions of the cholesterol synthetic inhibitor of the effective dose of active ingredient.
The present composition can be pharmaceutical composition or cosmetic composition.
Pharmaceutical composition of the present invention can be used for multiple indication, comprises common acne, psoriasis, the seborrheic dermatitis of scalp and saborea.
The invention further relates to cholesterol synthetic inhibitor such as HMG-CoA reductase inhibitor in treatment, relax or prevent the application of dermopathic surface drug preparation of compositions aspect.
The present invention also provides the method for improving skin, is included in skin surface and uses and to contain carrier and as the compositions of the cholesterol synthetic inhibitor of the effective dose of active ingredient.The concrete application of this method is treatment, relaxes or the prevention acne.
Term " effective dose " should be understood that to reach the average magnitude of the required active ingredient of required treatment or preventive effect.For example, the effective dose of cholesterol synthetic inhibitor is meant that the scope of application of this pharmaceutical composition under therapeutic scheme is enough to reach the consumption that improves skin in pharmaceutical composition of the present invention.
Being used for cholesterol synthetic inhibitor of the present invention is the various preparations that suppress any intermediate generation of each step of end-product such as cholesterol or mevalonate method, and wherein cholesterol is produced by precursor acetyl-CoA and acetoacetyl CoA.This inhibitor can be the inhibitor of inhibitory enzyme in each step, or as isolate intermediate preparation, the amount of the cholesterol that these two kinds of preparations all reduce this method and produced.
The preferred cholesterol synthetic inhibitor of the present invention is HMG-CoA reductase inhibitor such as lovastatin.
The preferably about 0.2-10% of the concentration of lovastatin, most preferably from about 2%.
This cholesterol synthetic inhibitor can with multiple other preparation such as antimicrobial, antibiotics for example, with treatment or prevention superinfection, decorticating agent, separately or the vitamin-A that is all-trans etc. that contains resorcinol be used from skin.
The carrier of the present composition can be any medicine or the available carrier of cosmetics, for example, and ethanol, gelatin, liposome dosage form, ointment, ointment etc.
Embodiment: I. preparation of compositions
Grind lovastatin capsule (Mevacor TM, Merck U.S.A.), by with 95% alcohol extraction active ingredient being separated and filtering, obtains the alcoholic solution of 2% lovastatin from excipient.II. clinical trial
In two clinical trials, test the efficient of above-mentioned preparation respectively.A. test 1
Pharmaceutical compositions subsurface every days two as mentioned above is used to suffer from two people's of common acne face, totally 12 weeks.Preceding 30 days of on-test,, needs of patients interrupted all other surface and the treatment of whole body anti-acne, treated and interrupted all facial cosmetics in preceding 7 days.
Before treatment beginning and behind the begin treatment 4,8 and 12 weeks by the whole acne lesion of record positions, comprise red and swollen acne position (pimple and pustule) and the acne position (white and black acne) of redness measure the acne situation.
The above-mentioned acne of all of two patients all be improved significantly, and the quantity of damage has reduced that half is many when treatment phase in 12 weeks finishes.May be owing to alcoholic acid reason, test have apparent side effect to slight exsiccant skin.B. test 2
4 patients of two men, two woman, the age is in 16-25 year, suffers from slightly to the moderate acne, uses above-mentioned preparation for treating.All medicines and cosmetics were stopped using 14 days, required every patient to use above-mentioned preparation then, every day twice, used for 8 weeks.Forbid adopting the treatment and the cosmetic of any other form during the treatment.The quantity at 4 and 8 week record acne positions (pimple, pustule, white and black acne) the results are shown in down tabulation 1 before treatment and after the treatment.The presentation of results of table 1,4 patients' of minimizing proof of all types of damage location quantity situation all improves.
The quantity at acne lesion position before table 1 treatment and during the treatment
The patient Damage Before the treatment Treated back 1 month Treated back 2 months
????1 White and the black acne of papulopustule ????10 ????11 ????18 ????7 ????3 ????10 ????3 ????2 ????7
????2 White and the black acne of papulopustule ????17 ????17 ????18 ????15 ????15 ????15 ????2 ????10 ????6
????3 White and the black acne of papulopustule ????7 ????12 ????22 ????2 ????7 ????14 ????- ????4 ????7
????4 White and the black acne of papulopustule ????20 ????16 ????15 ????18 ????9 ????10 ????5 ????5 ????5
On average White and the black acne of papulopustule ????13 ????14 ????18 ????10 ????8 ????12 ????2 ????5 ????6

Claims (14)

1. compositions that is used for skin surface contains carrier and as the cholesterol synthetic inhibitor of the effective dose of active ingredient.
2. according to the compositions of claim 1, be pharmaceutical composition.
3. according to the pharmaceutical composition of claim 2, wherein cholesterol synthetic inhibitor is 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor.
4. according to the pharmaceutical composition of claim 3, wherein inhibitor is a lovastatin.
5. according to the pharmaceutical composition of claim 4, wherein the concentration of lovastatin is about 0.2-10%.
6. according to the pharmaceutical composition of claim 5, wherein the concentration of lovastatin is about 2%.
7. according to the pharmaceutical composition in above-mentioned any claim, be used for the treatment of common acne, psoriasis, dermatosiss such as the seborrheic dermatitis of scalp and saborea.
8. according to the pharmaceutical composition that is used for the treatment of acne of claim 7, comprise following anti-acne formulations: antimicrobial, decorticating agent or various retinoeide.
9. cholesterol synthetic inhibitor is used for the preparation treatment, relaxes or prevent the purposes of dermopathic surface drug compositions.
10. according to the purposes of claim 9, wherein cholesterol synthetic inhibitor is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitor.
11. according to the purposes of claim 10, wherein inhibitor is a lovastatin.
12. a treatment relaxes or prevents dermopathic method, is included in the cholesterol synthetic inhibitor that skin surface uses effective dose.
13. according to the method for claim 12, wherein cholesterol synthetic inhibitor is 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) inhibitor.
14. according to the method for claim 13, wherein inhibitor is a lovastatin.
CN95195041A 1994-09-13 1995-09-13 Compositions for the treatment of skin disorders Expired - Fee Related CN1106841C (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL110943 1994-09-13
IL11094394A IL110943A (en) 1994-09-13 1994-09-13 Compositions comprising an inhibitor of cholesterol synthesis for the treatment of skin disorders

Publications (2)

Publication Number Publication Date
CN1158567A true CN1158567A (en) 1997-09-03
CN1106841C CN1106841C (en) 2003-04-30

Family

ID=11066547

Family Applications (1)

Application Number Title Priority Date Filing Date
CN95195041A Expired - Fee Related CN1106841C (en) 1994-09-13 1995-09-13 Compositions for the treatment of skin disorders

Country Status (14)

Country Link
US (1) US6126947A (en)
EP (1) EP0793489B9 (en)
JP (1) JP4128616B2 (en)
KR (1) KR970705990A (en)
CN (1) CN1106841C (en)
AT (1) ATE321548T1 (en)
AU (1) AU694274B2 (en)
BR (1) BR9509006A (en)
CA (1) CA2199844C (en)
DE (1) DE69534908T2 (en)
IL (1) IL110943A (en)
MX (1) MXPA97001884A (en)
RU (1) RU2159611C2 (en)
WO (1) WO1996008248A1 (en)

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AU3887399A (en) * 1998-05-05 1999-11-23 Saqib R. Anwel Hair and skin treatment method and composition
FR2801508B1 (en) * 1999-11-29 2003-11-14 Oreal USE OF HMG COA-REDUCTASE INHIBITORS FOR THE TREATMENT OF SEBORRHEA
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US20060111436A1 (en) * 2004-11-23 2006-05-25 John Griffin Compositions and treatments for modulating kinase and/or HMG-CoA reductase
US20070015779A1 (en) * 2005-04-29 2007-01-18 John Griffin Compositions and treatments for inhibiting kinase and/or hmg-coa reductase
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FR2954124B1 (en) * 2009-12-18 2012-04-06 Fabre Pierre Dermo Cosmetique USE OF 2,3-DIHYDROXYPROPYL DODECANOATE FOR THE TREATMENT OF SEBORRHEA
US20120149775A1 (en) * 2010-11-29 2012-06-14 Shiseido Company, Ltd. Methods for preventing and improving skin elastic property loss
US9273192B1 (en) * 2014-11-06 2016-03-01 George Reck Method of preventing microbial growth on water treatment dispersant
EP3355882A1 (en) 2015-10-01 2018-08-08 Kythera Biopharmaceuticals, Inc. Compositions comprising a statin for use in methods of adipolysis
AU2017351069B2 (en) 2016-10-24 2019-09-12 Colgate-Palmolive Company Oral care compositions and methods of use
JP2022036341A (en) * 2018-10-12 2022-03-08 学校法人慶應義塾 Pharmaceutical composition for treating chronic dermatitis

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Also Published As

Publication number Publication date
EP0793489A1 (en) 1997-09-10
EP0793489B9 (en) 2006-08-30
DE69534908D1 (en) 2006-05-18
ATE321548T1 (en) 2006-04-15
IL110943A0 (en) 1994-11-28
MXPA97001884A (en) 2004-04-16
RU2159611C2 (en) 2000-11-27
EP0793489B1 (en) 2006-03-29
WO1996008248A1 (en) 1996-03-21
CN1106841C (en) 2003-04-30
JP4128616B2 (en) 2008-07-30
DE69534908T2 (en) 2007-01-25
US6126947A (en) 2000-10-03
CA2199844C (en) 2007-04-10
CA2199844A1 (en) 1996-03-21
AU694274B2 (en) 1998-07-16
EP0793489A4 (en) 2001-12-19
JPH10505838A (en) 1998-06-09
IL110943A (en) 1997-02-18
AU3717395A (en) 1996-03-29
BR9509006A (en) 1998-06-23
KR970705990A (en) 1997-11-03

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